Journal
ENDOCRINE REVIEWS
Volume 26, Issue 3, Pages 465-478Publisher
ENDOCRINE SOC
DOI: 10.1210/er.2004-0027
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We have known for many years that estrogen is more than the female hormone. It is essential in the male gonads, and in both sexes, estrogen has functions in the skeleton and central nervous system, on behavior, and in the cardiovascular and immune systems. An important aspect of the discovery of estrogen receptor ( ER) beta is that the diverse functions of estrogen can now be divided into those mediated by ER alpha and those mediated by ER beta. Pharmacological exploitation of this division of the labors of estrogen is facilitated by the ligand-binding specificity and selective tissue distribution of the two ERs. Because the ligand binding domains of ER alpha and ER beta are significantly different from each other, selective ligands can be ( and have been) developed to target the estrogenic pathway that is malfunctioning, without interfering with the other estrogen-regulated pathways. Because of the absence of ER beta from the adult pituitary and endometrium, ER beta agonists can be used to target ER beta with no risk of adverse effects from chemical castration and uterine cancer. Some of the diseases in which there is hope that ER beta agonists will be of benefit are prostate cancer, autoimmune diseases, colon cancer, malignancies of the immune system, and neurodegeneration.
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